Effect of oral administration of folate sources on plasma folate levels in pigs: Comparison between reduced and oxidized forms of folate

Abstract

. Effect of oral administration of folate sources on plasma folate levels in pigs: Comparison between reduced and oxidized forms of folate. Can. J. Anim. Sci. 77: [497][498][499][500][501][502]. Two experiments were conducted to evaluate the response of plasma folate levels after oral administration of oxidized or reduced forms of folates, using seven Göttingen minipigs. Plasma folate levels, tetrahydrofolate (THF) and 5-methyltetrahydrofolate (5CH 3 -THF), were determined by high-performance liquid chromatography with electrochemical detection. In exp. 1, the absorption of the oxidized form of folate [(synthetic folic acid(FA)] and the reduced forms of folate (5-formyltetrahydrofolate (5HCO-THF), liver powder and digested bacterial cell powder (DBCP) were evaluated by measuring changes in plasma folate levels after a single oral administration. Liver powder and DBCP contained much reduced forms of folate. The administration of the reduced form of folates increased plasma THF levels while the levels of plasma THF and 5CH 3 -THF decreased after FA administration. In exp. 2, plasma folate levels were measured after long-term oral administration of FA for 30 d. Immediately after the beginning of the administration, the levels of both THF and 5CH 3 -THF decreased significantly and remained at a low level during the 30-d administration. Supplementation of sow feed with FA has been recommended in many countries improving reproductive performance. The present study, however, suggests that the oral administration of an oxidized form of folate, FA, may not be as effective as previously thought, and the reduced forms of folate might be preferable for the supplementation of pig feeds. Sci. 77: 497-502. Deux expériences avaient pour objet d'évaluer la réponse des concentrations plasmatiques de folates à l'administration orale à des porcs miniatures Göttingen de folate dans la forme réduite ou dans la forme oxydée. Les concentrations plasmatiques des folates, tétrahydrofolate (THF) et méthyle-5 tétrahydrofolate (CH 3 -5THF) étaient mesurées par HPLC à détection électrochimique. Dans la première expérience l'absorption d'une forme oxydée (acide folique de synthèse AF) et d'une forme réduite formyl-5 tétrahydrofolate (HCO-5THF) ainsi que de poudre de foie et de poudre de digesta de cellules bactériennes (PDCB) était comparée quant à l'effet sur les modifications des taux plasmatiques de folate après une seule administration orale. La poudre de foie et la PDCB contenaient beaucoup de folate sous la forme réduite. L'administration de folate réduit donnait lieu à un accroissement des taux plasmatiques de THF, tandis que celle de la forme oxydée (AF) abaissait les concentrations de THF et de CH 3 -5THF. Dans la deuxième expérience, les niveaux plasmatiques de folate étaient mesurés après des administrations journalières de AF répétées pendant 30 jours. Dès le début, on observait une chute significative des concentrations de THF et de CH 3 -5THF qui se maintenaient ensuite à ces niveaux tout au long de l'expérience. Beaucoup de pay...

Comparison of Dihydrofolate Reductase Activities for Folic Acid in Pigs and Rats Using In Vivo and In Vitro Evaluation Techniques.

“…These findings from in vivo and in vitro experiments demonstrate that the DHFR activity for PteGlu in pigs was much less than that in rats. The low DHFR activity in pigs may be one of the causal factors of the fact that the plasma H4PteGlu and 5-CH3-H4PteGlu did not in crease after oral administration of PteGlu, even at high dose (4,13). The reduction of PteGlu to H2PteGlu in pigs may be regarded as the rate-limiting step for the re duction of PteGlu to H4PteGlu, because the Vmax of pig liver DHFR for PteGlu was remarkably small, compared with that for H2PteGlu ( Table 3).…”

Níveis de ácido fólico em dietas contendo ácido fórmico para leitões de 21 a 48 dias de idade

“…Esses pesquisadores sugeriram três hipóteses para esse evento e que podem também justificar a tendência de diminuição do folato sérico neste experimento: 1) inibição competitiva na absorção intestinal do ácido fólico com folatos endógenos derivados da circulação enterohepática, visto que grandes quantidades de folatos endógenos são recicladas por esta circulação (Steinberg, 1984;Shin et al, 1995) e absorvidas ativamente na mucosa intestinal; 2) competição de ligação do ácido fólico sobre o tetrahidrofolato para a proteína de ligação de folato no plasma (o ácido fólico entrando no sistema circulatório pode libertar tetrahidrofolato do sítio de ligação de proteína de ligação de folatos, expondo o tetrahidrofolato à possível degradação na circulação e/ou melhorando a eficiência renal de liberação de tetrahidrofolato); e 3) reduzida conversão de ácido fólico para folato reduzido, ou seja, baixa atividade de folato redutas no fígado de suínos, uma vez que administração de dihidrifolato aumenta os níveis de folatos no plasma, o que não ocorre com o ácido fólico (Mizuno et al, 1997). Essas hipóteses também podem ser apontadas para justificar a ausência de correlação entre os valores de folato sérico e o aumento de suplementação de ácido fólico neste experimento, uma vez que a metodologia empregada quantifica folatos totais e não especifica as formas oxidadas e reduzidas.…”

Plasma reduced folates, reproductive performance, and conceptus development in sows in response to supplementation with oxidizedand reduced sources of folic acid1

“…It is possible that intestinal reduction of folates is more efficient under limit-feeding conditions, but this point cannot be determined from these data. Using mature, nonpregnant miniature pigs, Mizuno et al (1997) have presented data indicating that oral supplements of THFA and a bacterial cell powder rich in reduced folates were more effective than pteroylmonoglutamate (oxidized) folate in elevating plasma THF. Furthermore, it has been demonstrated in rats that intestinal absorption of 5-MF is inhibited by the pteroylmonoglutamate form of the vitamin (Kudo et al, 1995).…”

“…In previous studies, the oxidized or pteroylmonoglutamate form of the vitamin has been used, but in vivo, the reduced forms dihydrofolate and tetrahydrofolate function in single-carbon transfer reactions for nucleic acid synthesis and amino acid metabolism (Krumdieck, 1990). Mizuno et al (1997) reported that oral supplementation of pigs with tetrahydrofolic acid or a bacterial cell powder rich in reduced folates was more effective than an oxidized source in elevating plasma reduced folates. Considering these factors, reduced sources of supplemental folate may produce greater litter size responses in sows than the pteroylmonoglutamate traditionally supplemented.…”